Obesity is a growing problem in the developed world and underlies chronic co-morbidities that reduce overall life expectancy (e.g., hypertension and diabetes). While 25% or more of adults admitted to intensive care units (ICU) in the United States and other developed countries are overweight or obese, whether this negatively impacts ICU outcomes is unclear. This point is highlighted by conflicting data regarding obesitys effects on mortality in patients with bacterial infection and sepsis or viral influenza, two common reasons for ICU admission. Although several studies suggest that obesity worsens or has no impact on survival in patients with sepsis, two recent systematic reviews and meta-analyses both reported that overweight or obese body-mass indices (BMI) were paradoxically associated with improved outcomes in sepsis. By contrast, two other systematic reviews and meta-analyses found that for patients with influenza pneumonia, obesity increased the risk of either a combined end point of ICU admission and death or death alone. Another pooled analysis found that obesity increased the risk of death with influenza and pneumonia. Research into the mechanisms and effects of obesity has relied on both diet and genetically (e.g., leptin or leptin-receptor deficient mice) induced animal obesity models. These models have also been used to examine the impact of obesity on the host response and outcome in conditions associated with critical illness, including bacterial and viral infection. In contrast to clinical studies examining these questions which are typically observational and retrospective and possibly confounded by differing baseline characteristics and methodology, animal studies employ prospective controlled designs and uniform subjects that differ primarily in body weight and obesity cause. We therefore performed a systematic review and meta-analysis of animal studies to further examine how obesity may impact survival with bacterial or influenza infection. Across the studies examined, obesity was closely associated with increased mortality in both bacteria and virus challenged animal models. An analysis of these studies suggests several reasons why there may be a disparity between the apparent effects of obesity in humans with sepsis and in animal sepsis models. A manuscript has been completed and is presently under review.